Project Summary/Abstract Cervical cancer is the second most common malignancy among women worldwide. It is estimated that in 2007, 3,670 deaths will occur in the United States alone from this disease and 11,150 new cases of invasive cervical cancer will be diagnosed. Although early detection of cervical precancer has played a central role in reducing the mortality associated with this disease over the last 50 years, the incidence of pre-invasive squamous carcinoma of the cervix. When cervical cancers are detected early, they are highly curable. Existing screening and detection techniques, the Pap smear and colposcopy, have several deficiencies that prevent efficient management of an otherwise controllable disease. An automated diagnostic method with improved sensitivity and specificity that could allow for a See and Treat protocol would significantly improve the management of the disease. This proposal seeks to prove the hypothesis that Raman spectroscopy, can provide differential diagnosis of cervical precancers, both high and low grade from inflammation, squamous metaplasia and normal areas of the cervix. The main objective of this proposal is to characterize and validate that low grade lesions can be differentiate from high grade lesions as well as the normal cervix and that this diagnosis can be performed regardless of the menopausal status of the patient. This will be accomplished by conducting a large clinical investigation, collecting Raman spectra from both normal and diseases cervix, separating them by histological category and classifying them via a multi-class discrimination algorithm. Additionally, with the development of a unique model for tissue spectral signatures, we seek to use this model to understand the disease process as it applies to optical spectroscopy. Finally, the system will be updated to be as compact as possible and the software developed to be easy (one click collection and classification of a spectra) for clinical use. The results of the proposed work will have a significant impact on health care by providing the potential for complete disease management with a single detection tool. This would result in improved patient care and cost-effectiveness. With the success of this technique, Raman spectroscopy can be applied to other organ sites such as the prostate and ovary as well as other diseases thus impacting a broader field in medicine.